Hypersensitivity Reactions

Immune mediated reactions causing tissue injury in response to an otherwise harmless antigen, classified by the Gell and Coombs system into four types based on the underlying immunological mechanism, providing a framework for understanding the pathophysiology, timing and management of a wide range of clinical conditions.

Classification

Type one, immediate hypersensitivity, is IgE mediated, with antigen binding to IgE on the surface of mast cells and basophils triggering rapid degranulation and release of histamine and other mediators, producing reactions within minutes, as seen in anaphylaxis, allergic rhinitis and food allergy.

Type two, cytotoxic hypersensitivity, involves IgG or IgM antibodies directed against antigens on the surface of specific cells, activating complement and cell mediated cytotoxicity, as seen in autoimmune haemolytic anaemia, haemolytic transfusion reactions and Goodpasture syndrome.

Type three, immune complex hypersensitivity, involves circulating antigen antibody complexes depositing in tissues and activating complement, producing inflammation, as seen in serum sickness, certain vasculitides and some manifestations of systemic lupus erythematosus.

Type four, delayed type hypersensitivity, is T cell mediated rather than antibody mediated, developing over one to several days as sensitised T cells recruit and activate macrophages, as seen in allergic contact dermatitis, tuberculin skin reactions and many drug induced severe cutaneous reactions.

Type one reactions present rapidly, within minutes to a few hours of exposure, with urticaria, angioedema, bronchospasm, gastrointestinal symptoms and, in severe cases, anaphylaxis with cardiovascular collapse.

Type two reactions present with symptoms reflecting destruction of the targeted cell type, such as anaemia and jaundice in haemolytic reactions, or organ specific dysfunction where the target antigen is tissue bound.

Type three reactions typically present days to weeks after antigen exposure, with fever, rash, arthralgia and, depending on the site of immune complex deposition, organ specific involvement such as glomerulonephritis or vasculitis.

Type four reactions develop over one to several days following exposure, presenting as localised eczematous or indurated skin reactions in contact dermatitis, or, in severe drug reactions, widespread cutaneous eruption with potential mucosal and systemic involvement.

Recognising the timing of onset relative to exposure, together with the specific clinical pattern, is central to identifying the likely underlying hypersensitivity mechanism and guiding both diagnosis and management.

Diagnosis is predominantly clinical, based on a careful history establishing the temporal relationship between exposure to a suspected trigger and the onset of symptoms, together with the specific pattern of clinical features.

Specific IgE testing (skin prick testing or serum specific IgE) supports the diagnosis of type one reactions and identifies the responsible allergen where relevant.

Direct antiglobulin testing and identification of the specific autoantibody or alloantibody support diagnosis of type two reactions.

Complement levels (often reduced during active immune complex deposition), circulating immune complex assays where available, and identification of the causative antigen support diagnosis of type three reactions.

Patch testing is the diagnostic test of choice for type four contact hypersensitivity reactions, identifying the specific responsible allergen.

Tissue biopsy, where performed, can support the diagnosis and help exclude alternative causes across all four types, with the specific histological pattern reflecting the underlying immunological mechanism.

Avoidance of the identified trigger is the cornerstone of management across all four types of hypersensitivity reaction once the causative antigen has been identified.

Acute type one reactions are managed with antihistamines for mild disease, and with adrenaline, corticosteroids and supportive care for anaphylaxis.

Type two reactions are managed by treating the underlying cause where identifiable, together with corticosteroids or other immunosuppression, and supportive management of the resulting cytopenia or organ dysfunction, with transfusion support where appropriate for severe haemolysis.

Type three reactions are managed by removing the causative antigen where possible, together with corticosteroids or other immunosuppression for significant inflammation, with plasma exchange considered for severe immune complex mediated disease.

Type four reactions are managed with topical or systemic corticosteroids according to severity, together with strict avoidance of the identified allergen, and severe drug induced type four reactions require immediate cessation of the causative medication and, in severe cutaneous adverse reactions, specialist multidisciplinary supportive care.

Desensitisation protocols are available for selected type one reactions where avoidance is not feasible and ongoing exposure to the antigen is clinically necessary, performed under close specialist supervision given the risk of provoking a significant reaction during the process.

Patient education regarding trigger avoidance, recognition of early symptoms of a reaction, and, where relevant, emergency treatment (adrenaline autoinjector training for those at risk of anaphylaxis) forms an essential and often underemphasised component of long term management across this group of conditions.